Prostate cancer is one of the most preventable cancers, yet effective therapeutics, especially targeted therapy, are still lacking. Saponin has been reported to possess various biological properties such as anti-cancer and anti-inflammatory activity. In this study, the anti-tumor activity of magnetic nanoparticles loaded with ethylene glycol and a saponin complex (ESMP) against DU145 prostate cancer cells was examined. Composite nanoparticles with an average size of 23 nm were prepared using a chemical co-precipitation technique. The ESMP were cytotoxic to DU145 cells and specifically inhibited cell proliferation. In contrast, the magnetic nanoparticles by themselves showed no significant cytotoxicity. The expression levels of the angiogenesis related proteins, including phospho-extracellular signal-regulated kinase, p38 and pAKT, decreased after ESMP treatment. This study highlights the therapeutic potential of using ESMP for targeted-therapy against prostate cancer.